Revisiting the effects of Cas9 on p53-inactivating mutations reveals sex-biased genome editing by CRISPR-Cas9

Abstract

AbstractEnache et al. report that Cas9 alone can activate the p53 pathway and select for p53-inactivating mutations. We reanalyzed TP53 mutations in Parental-cells (no introduction of Cas9) and Cas9-cells (Cas9-expressing derivatives) from the Enache et al. study and found significantly shrinking inactivating subclonal mutations of TP53 in Cas9-cells, which means Cas9 also selects against TP53-inactivating mutations. We also examined the sex-biased effect of Cas9, which was implied in their results but was not noticed and discussed by Enache et al. We further highlighted the sex bias in large-scale CRISPR-Cas9 screening experiments in various cell lineages. We suggest the sex bias effect may need to be considered in future clinical applications using CRISPR-Cas9.